The proposed research concerns pathogenetic mechanisms in certain disorders by hematopoiesis and involves 2 areas of investigation - 1. Drug-induced bone marrow injury as exemplified by chloramphenicol (CAP)-induced marrow damage. Emphasis will be directed at the molecular mechanisms underlying the common reversible erythroid suppression from CAP and the more devastating complication of aplastic anemia. The nature of the mitochondrial lesion from CAP will be studied. Attempts will be made to uncover a predisposition in individuals susceptible to CAP aplastic anemia by studying the in vitro effect of the drug on bone marrow from patients who have recovered from this complication. 2. Elucidate the role of cytoplasmic DNA and RNA polymerases in the regulation of gene expression in erythroid cells. This objective will be approached by further purification and characterization of these polymerases, their endogenous templates and their product from both bone marrow erythroblasts and peripheral reticulocytes. 3. Studies on leukocyte alkaline phosphatase (AP) with the aim of elucidating the factors responsible for the switch on and off of AP synthesis in cultured rat chloroma cells.